Current diagnostic brain imaging devices such as CT, MRI, PET scan, and fMRI can be useful in detecting anomaly in patients with traumatic brain injuries. However, most cases of the brain trauma produce mild traumatic brain injuries (mTBI) such as a concussion. These conditions are not detectable with routine diagnostic brain imaging devices. For example, diffuse axonal injury is one of the most prevalent damage in mTBI. Yet, most clinical imaging techniques cannot capture diffuse pathological axonal injuries. In cases of brain trauma that produced significant focal brain damages visible on diagnostic images, the symptoms, sequelae, recovery, and long term outcomes often do not correlate with the severity of brain damage as defined by the imaging techniques, indicating other factors may have greater bearing on symptomology and brain pathology. Indeed, brain cadaver studies have revealed common and extensive axonal disruption, perivascular astrocyte tangles, and neurofibrillary tangles in brains with concussion history and chronic symptoms. Evidence from in vivo studies also show that the extent of white matter abnormalities after mTBI correlates with the severity of post-concussion cognitive problems.
The prevalence of mTBI and sometime devastating long term consequence of concussions illustrate the needs for more sensitive and objective tests. In Canada, the yearly incidents of concussion are estimated to be 160,000 cases while in USA the annual incidents of mTBI approach one million. mTBI impacts diverse brain functions that include cognition, emotion, motor control, sensation, and neuro-behaviors. Although repertoire and severity of concussion effects varies, the sequalae of concussion can be debilitative particularly among at risk groups such as younger individuals, athletes, and military personnel.
mTBI also increase risks to developing dementia, early senility, Parkinson's disease, and Alzheimer's disease. Although underlining etiology and pathology differ, these diseases or disorders share motor dysfunctions and cognitive impairment with mTBI. Several studies have demonstrated that a more rapid rate of motor decline in cognitively intact individuals predicted the subsequent development of mild cognitive impairment and Alzheimer's disease, and loss of motor function can precede cognitive impairment (see Aron S Buchman and David A Bennett. Loss of motor function in preclinical Alzheimer's disease. Expert Rev Neurother. 2011 May; 11(5): 665-676).
Repetitive brain trauma may also lead to chronic traumatic encephalopathy, a progressive neurodegenerative disease that expresses a wide range of symptoms including motor deficits, cognitive impairment, depression, and violent mood alteration. According to autopsy studies on brains of deceased former National Football League players, 95% of those brains had chronic traumatic encephalopathy that is marked by wide-spread neurofibrillary tangles and perivascular astrocyte tangles as well as significant deposits of neurodegenerative biomarkers. However, currently, the condition of chronic traumatic encephalopathy can only be diagnosed by post-mortem autopsy.
One of challenges in mTBI diagnosis, prognosis, and management is the lack of a practical and objective diagnostic test. Currently, a concussion may be recognized based on observation and assessment of overt signs and symptoms. However, there remain the needs for improvements on many clinical related issues such as under-diagnosis of concussion, identification of impaired functional regions of the brain, determinations of severity and recovery progress, and correlation of brain injury with symptomology. Furthermore, a lack of objective and sensitive test for brain injury leads to repetitive injuries in athletes and increases the risk for developing long-term effects of brain injury such as chronic traumatic encephalopathy and other neurodegenerative diseases. The development of a sensitive test for mTBI may provide a useful tool that will help to solve some of these clinical dilemmas.
It is the object of the present invention to address the deficiencies of the prior art. The principle and strategy deployed in this invention to provide the mTBI diagnosis have not be applied or reported before.